9alpha-Fluorocortisol

9alpha-Fluorocortisol Uses, Dosage, Side Effects, Food Interaction and all others data.

9alpha-Fluorocortisol is a synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity. It is indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. The physiologic action of fludrocortisone acetate is similar to that of hydrocortisone. However, the effects of fludrocortisone acetate, particularly on electrolyte balance, but also on carbohydrate metabolism, are considerably heightened and prolonged. Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions.

9alpha-Fluorocortisol binds the mineralocorticoid receptor (aldosterone receptor). This binding (or activation of the mineralocorticoid receptor by fludrocortisone) in turn causes an increase in ion and water transport and thus raises extracellular fluid volume and blood pressure and lowers potassium levels.

9alpha-Fluorocortisol is a synthetic mineralocorticoid used to replace endogenous aldosterone in conditions resulting in missing or inadequate endogenous synthesis. It acts on the kidneys to increase both sodium reabsorption and potassium excretion. As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days despite a relatively short plasma half-life. Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.

9alpha-Fluorocortisol
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	9alpha-Fluorocortisol
Availability	Prescription only
Generic	Fludrocortisone
Fludrocortisone Other Names	9alpha-Fluorocortisol, Fludrocortison, Fludrocortisona, Fludrocortisone, Fludrocortisonum, Fluohydrocortisone
Related Drugs	prednisone, dexamethasone, methylprednisolone, hydrocortisone, Medrol, Decadron, Medrol Dosepak, Florinef, Cortef
Type
Formula	C₂₁H₂₉FO₅
Weight	Average: 380.4504 Monoisotopic: 380.199902243
Protein binding	Fludrocortisone is 70-80% protein bound in plasma, mostly to albumin and corticosteroid-binding globulin.
Groups	Approved, Investigational
Therapeutic Class	Corticosteroid
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Used for oral mineralocorticoid replacement therapy in:

Primary and secondary adrenocortical insufficiency in Addison’s disease
Salt losing adrenogenital syndrome
Postural hypotension

9alpha-Fluorocortisol is also used to associated treatment for these conditions: Otitis Externa, Otitis Media (OM), Primary adrenocortical insufficiency, Secondary adrenocortical insufficiency, Salt-losing Androgenital syndrome

How 9alpha-Fluorocortisol works

The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure. In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone.

9alpha-Fluorocortisol binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na^{+ These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. 9alpha-Fluorocortisol may also exert a direct effect on plasma sodium levels via action at the Na⁺}

9alpha-Fluorocortisol also acts on glucocorticoid receptors, albeit with a much lower affinity - the glucocorticoid potency of fludrocortisone is approximately 5-10 times that of endogenous cortisol, whereas its mineralocorticoid potency is 200-400 times greater.

Dosage

9alpha-Fluorocortisol dosage

Primary and secondary Adrenocortical Insufficiency in Addison’s disease: Usual dose may range from 0.2 mg 3 times weekly to 0.2 mg daily. If hypertension occurs, reduce dosage to 0.05 mg daily. Administer concomitantly with Cortisone or hydrocortisone.

Salt-Losing Adrenogenital Syndrome: 0.1 to 0.2 mg/day.

Postural Hypotension: 0.1-0.4 mg daily to diabetic patients with postural hypotension; 0.05-0.2 mg daily to patients with postural hypotension secondary to Levodopa therapy.

Side Effects

Most adverse reactions are caused by the drug’s mineralocorticoid activity (retention of sodium andwater) include erythema, purpura, vertigo, pancreatitis, increased intraocular pressure, muscular weakness, hypertension, edema, cardiac enlargement, congestive heart failure, steroid myopathy, peptic ulcer, osteoporosis, convulsions, menstrual irregularities, potassium loss, hypokalemic alkalosis, allergic and anaphylactic reaction etc. When 9alpha-Fluorocortisols is used in the small dosages recommended, side effects are not usually a problem; however the above mentioned unwanted effects should be kept in mind, particularly when 9alpha-Fluorocortisols is used over a prolonged period of time or in conjunction with cortisone or a similar glucocorticoid.

Toxicity

The oral LD₅₀ of fludrocortisone in rats is >1g/kg. Acute overdosage of fludrocortisone is likely to result in symptoms consistent with its adverse effect profile. Patients receiving a single large dose should be treated with plenty of water by mouth and should undergo monitoring of serum electrolytes, particularly potassium and sodium, and be treated appropriately for any developing imbalances.

Precaution

Because of its marked effect on sodium retention, the use of 9alpha-Fluorocortisol in the treatment of conditions other than those indicated herein is not advised. 9alpha-Fluorocortisol should be used with caution in patients suffering from different infections (like tuberculosis, measles, chicken pox, herpes zoster or threadworm infestation), congestive cardiac failure, hypertension, renal insufficiency, osteoporosis, drug-induced secondary adrenocortical insufficiency, peptic ulcer, intestinal anastomosis and ulcerative colitis.

Interaction

Interactions can occur with following drugs: Amphotericin B, potassium depleting diuretics, anticholinesterases, anticoagulants, antidiabetics. Antitubercular drugs, cyclosporine, digitalis glycosides, oral contraceptives and ketoconazole .

Food Interaction

Limit salt intake. Excessive intake of salt can result in hypertension and edema.

9alpha-Fluorocortisol Cholesterol interaction

[Moderate] Corticosteroids may elevate serum triglyceride and LDL cholesterol levels if used for longer than brief periods.

Patients with preexisting hyperlipidemia may require closer monitoring during prolonged corticosteroid therapy, and adjustments made accordingly in their lipid-lowering regimen.

9alpha-Fluorocortisol Hypertension interaction

[Moderate] Corticosteroids may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure.

These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone.

The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities.

However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods.

Therapy with corticosteroids should be administered cautiously in patients with preexisting fluid retention, hypertension, congestive heart failure, and

Dietary sodium restriction and potassium supplementation may be advisable.

9alpha-Fluorocortisol Drug Interaction

Unknown: diphenhydramine, diphenhydramine, duloxetine, duloxetine, pregabalin, pregabalin, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, ondansetron, ondansetron, cetirizine, cetirizine

9alpha-Fluorocortisol Disease Interaction

Major: GI perforation, infections, PUD, vaccinationModerate: (+) tuberculin test, cirrhosis, depression/psychoses, diabetes, electrolyte imbalance, fluid retention, hyperadrenocorticalism, hyperlipidemia, hypothyroidism, liver disease, MI, myasthenia gravis, myopathy, ocular herpes simplex, ocular toxicities, osteoporosis, scleroderma, strongyloidiasis, thromboembolism

Volume of Distribution

The apparent volume of distribution of fludrocortisone is 80-85 L. Distribution into CSF appears minimal - the observed ratio of CSF drug concentration versus plasma drug concentration is 1:6.

Elimination Route

Absorption of fludrocortisone following oral administration is rapid and complete. Pharmacokinetic studies have estimated the C_max to be 0.0012 to 0.20 μg/L with a T_max between 0.5 and 2 hours. The AUC_0-∞ of fludrocortisone after oral administration has been variably estimated to be between 1.22 to 3.07 μg.h/L.

Half Life

The plasma half-life of fludrocortisone has been variably reported to be between 1-3.5 hours, though prescribing information gives an approximate half-life of 18-36 hours.

Clearance

Population pharmacokinetics have estimated the plasma clearance of fludrocortisone to be 40.8 L/h.

Elimination Route

Approximately 80% of an administered dose of fludrocortisone shows up in the urine, with the other 20% likely eliminated via fecal or biliary route.

Pregnancy & Breastfeeding use

Pregnancy category C. There are no adequate and well-controlled studies in pregnant women. 9alpha-Fluorocortisol is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.

Lactation: There are no data on the excretion of fludrocortisone into human milk. However, corticosteroids (systemic therapy) are distributed into breast milk and could cause growth suppression and/or other adverse effects in nursing infants. The manufacturer recommends that caution be used when administering 9alpha-Fluorocortisol to nursing women.

Contraindication

In case of adrenal insufficiency, no absolute contraindications are applicable. In the treatment of non-endocrine diseases where pharmacological dose are more likely to be used, the contraindications to be considered carefully. Relative contraindications include: systemic fungal infection, hypersensitivity to 9alpha-Fluorocortisol, diabetic mellitus, osteoporosis and acute infection.